Protein O-mannosylation is crucial for E-cadherin-mediated cell adhesion

Proc Natl Acad Sci U S A. 2013 Dec 24;110(52):21024-9. doi: 10.1073/pnas.1316753110. Epub 2013 Dec 2.


In recent years protein O-mannosylation has become a focus of attention as a pathomechanism underlying severe congenital muscular dystrophies associated with neuronal migration defects. A key feature of these disorders is the lack of O-mannosyl glycans on α-dystroglycan, resulting in abnormal basement membrane formation. Additional functions of O-mannosylation are still largely unknown. Here, we identify the essential cell-cell adhesion glycoprotein epithelial (E)-cadherin as an O-mannosylated protein and establish a functional link between O-mannosyl glycans and cadherin-mediated cell-cell adhesion. By genetically and pharmacologically blocking protein O-mannosyltransferases, we found that this posttranslational modification is essential for preimplantation development of the mouse embryo. O-mannosylation-deficient embryos failed to proceed from the morula to the blastocyst stage because of defects in the molecular architecture of cell-cell contact sites, including the adherens and tight junctions. Using mass spectrometry, we demonstrate that O-mannosyl glycans are present on E-cadherin, the major cell-adhesion molecule of blastomeres, and present evidence that this modification is generally conserved in cadherins. Further, the use of newly raised antibodies specific for an O-mannosyl-conjugated epitope revealed that these glycans are present on early mouse embryos. Finally, our cell-aggregation assays demonstrated that O-mannosyl glycans are crucial for cadherin-based cell adhesion. Our results redefine the significance of O-mannosylation in humans and other mammals, showing the immense impact of cadherins on normal as well as pathogenic cell behavior.

Keywords: O-glycans; POMT1; POMT2; mouse preimplantation development; protein-glycosylation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adherens Junctions / metabolism*
  • Animals
  • Cadherins / metabolism*
  • Cell Adhesion / physiology*
  • DNA Primers / genetics
  • Dogs
  • Embryo, Mammalian / cytology*
  • Embryo, Mammalian / physiology
  • Embryonic Development / physiology*
  • Fluorescent Antibody Technique
  • Glycosylation
  • Madin Darby Canine Kidney Cells
  • Mannose / metabolism*
  • Mass Spectrometry
  • Mice
  • Polysaccharides / metabolism


  • Cadherins
  • DNA Primers
  • Polysaccharides
  • Mannose